Regulatory T cells (Tregs) have long been thought to exert protective, immunoinhibitory functions in the C3H/HeJ mouse model of alopecia areata (AA), while their role in human AA remains obscure. However, FOXP3+/γdT cell receptor+ Tregs (γdTregs) may be the predominant and more potently immunoinhibitory regulatory T cells. Given that we have recently identified γdT cells as important novel players in human AA pathobiology, we have therefore asked whether γdTregs play a role in human AA and might be recruited for future AA treatment. Autologous circulating human γdTregs were generated by culture of PBMC's with IL-2, IL-15 and zoledronate for 7 days and thereafter the cultured cells were sorted by FACSAria by using anti-CD3 and anti-γδTCR antibodies. γdTregs were characterized by FACS, ELISA and cell division analyses. The cells were either injected ID into experimentally induced AA lesions on human scalp skin xenotransplants on SCID/beige mice, or co-incubated with organ-cultured, stressed human scalp hair follicles (HFs) that exhibit partial HF immune privilege (IP) collapse. 50 days after γdTreg injection in vivo, impressive hair regrowth was observed in all examined human xenotransplants, along with a significantly reduced perifollicular infiltrate and HF IP restoration. Ex vivo, γdTregs significantly reduced premature catagen and IP collapse induction (HLA-ABC up-regulation) by co-culture with activated CD8+/NKG2D+ T cells(p<0.01). Importantly, γdTregs also significantly reduced AA-associated “danger” signals (MICA/B, CD1d), increased proliferation and decreased apoptosis of hair matrix keratinocytes and increased the expression of HF IP guardians (TGF-β1, α-MSH) in the outer root sheath. Collectively this shows that autologous, blood-derived human γdTregs exert potent protective resp. therapeutic effects on AA-affected human scalp HFs ex vivo and in vivo and thus deserve full clinical exploration as novel cell-based therapy in future AA management

ESDR004 - Cell-based therapy may be effective in alopecia areata: Preclinical evidence that autologous, peripheral regulatory γdT cells are preventive in human ex vivo and therapeutic in human in vivo models

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.